The purpose is to establish the neurobiological substrate of developmental stuttering using genetic linkage techniques. The goal is to identify gene products which may be used to develop neuroimaging techniques, which themselves may be used to characterize the neurobiology of developmental stuttering. The first arm of this project involves genetic linkage analysis in large multiplex families with members from several generations who stutter. This study represents a collaboration with Mark Leppert of the University of Utah. We are evaluating a large multigenerational kindred with branches in Idaho, Utah and Maine and a second large kindred in Texas. Phenotyping has been completed and genotyping is now underway. As a result of publicizing the study among speech-language pathologists specializing in fluency disorders, we have ascertained a number of additional kindreds whose members have agreed to participate. The second arm of this project involves candidate gene analyses, evaluating the frequencies of DNA polymorphisms for which gene products represent neurotransmitter receptors or rate-limiting synthetic enzymes of central serotonin and dopamine systems. Individuals who have previously participated in other stuttering-related programs of the Section and their parents are being studied. Blood samples have been collected and DNA extracted from approximately 30 individuals who have consented to participate. Recruitment continues for this portion of the study.